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10.1172/jci.insight.148003 http://scihub22266oqcxt.onion/10.1172/jci.insight.148003 34357881!8492301!34357881     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       JCI+Insight 2021 ; 6 (18): ä Nephropedia Template TP {{tp|p=34357881|t=2021. Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses |pdf=|usr=}}{{34357881}} gab.com Text Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=34357881 #FOAvip Cell lines are the mainstay in understanding the biology of COVID-19 infection but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue would allow for the ex vivo study of the interindividual heterogeneity of host response to SARS-CoV-2, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 21 donors, many of whom had clinical risk factors for severe COVID-19. Cryopreserved tissues preserved 90% cell viability and contained heterogenous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infected with HCoV-OC43 and SARS-CoV-2 and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL6, CXCL8, and IFNB1 in response to SARS-CoV-2. Treatment of tissues with dexamethasone and the experimental drug N-hydroxycytidine suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted but unproven antiviral activity, each suppressed viral replication in tissues from a subset of donors. In summary, we developed a system for the ex vivo study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis. Twit Text FOAVip Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=34357881 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34357881 #FOAvip English Wikipedia <ref>{{Cite pmid|34357881}}</ref> Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses #MMPMID34357881 Schaller MA; Sharma Y; Dupee Z; Nguyen D; Uruena J; Smolchek R; Loeb JC; Machuca TN; Lednicky JA; Odde DJ; Campbell RF; Sawyer WG; Mehrad B JCI Insight 2021[Sep]; 6 (18): ä PMID34357881show ga Cell lines are the mainstay in understanding the biology of COVID-19 infection but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue would allow for the ex vivo study of the interindividual heterogeneity of host response to SARS-CoV-2, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 21 donors, many of whom had clinical risk factors for severe COVID-19. Cryopreserved tissues preserved 90% cell viability and contained heterogenous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infected with HCoV-OC43 and SARS-CoV-2 and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL6, CXCL8, and IFNB1 in response to SARS-CoV-2. Treatment of tissues with dexamethasone and the experimental drug N-hydroxycytidine suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted but unproven antiviral activity, each suppressed viral replication in tissues from a subset of donors. In summary, we developed a system for the ex vivo study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis. |*COVID-19 Drug Treatment[MESH] |*SARS-CoV-2[MESH] |Aged[MESH] |Antiviral Agents/*therapeutic use[MESH] |COVID-19/immunology[MESH] |Cell Line[MESH] |Female[MESH] |Humans[MESH] |Immunity, Innate/*immunology[MESH] |Interferons/*therapeutic use[MESH] |Lung/immunology/*pathology[MESH] |Male[MESH]Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host (epmc).pdf DeepDyve Pubget Overpricing